DE102004028156A1 - Combination of radio waves and one or more of monoclonal antibodies, tyrosine-kinase inhibitors, angiogenesisi inhibitors, farnesyl transferase inhibitors, topoisomerase - I or II inhibitors, cytokine and antisense oligonucleotides - Google Patents

Abstract

The combination of radio waves and one or more active material chosen from: monoclonal antibodies, tyrosine-kinase inhibitors, angiogenesisi inhibitors, farnesyl transferase inhibitors, topoisomerase -I or II inhibitors, cytokine and antisense oligonucleotides is claimed. Independent claims are included for: (1) use of the combination for prevention and treatment of cancer, malignant and benign tumors and metastases; (2) use of radio waves to increase the activity of monoclonal antibodies, tyrosine-kinase inhibitors, angiogenesis inhibitors, farnesyl transferase inhibitors, topoisomerase -I or II inhibitors, cytokine, antisense oligonucleotides and chemotherapeutics; (3) use of radio waves to reduce the side effects of chemotherapeutics; and (4) prevention and treatment of cancer, malignant and benign tumors and metastases using the combination.

Description

The The invention relates to a combination of radio waves with pharmacological active substances. The combination according to the invention can furthermore still include chemotherapeutic agents and is preferred for prophylaxis and / or treatment of tumors and metastases.

The Therapy of cancer with different radiation methods is long known and state of the art. These include, among other things, the irradiation with X-rays, gamma radiation and with less energetic radiation such as microwave.

• 1. Mikrowelle, Frequenzbereich 400 bis 2500 MHz
• 2. Ultraschall, Frequenzbereich 0,5 bis 5 MHz
• 3. Radiofrequenz, Frequenzbereich 3 bis 300 MHz
• 4. „Hot-Source"- Hyperthermie, Heisswasser
• 5. Laser

In addition to irradiation with high-energy X-rays or radioactive radiation, there are alternative techniques to treat electromagnetic radiation tissue:

• 1. Microwave, frequency range 400 to 2500 MHz
• 2. Ultrasound, frequency range 0.5 to 5 MHz
• 3. Radio frequency, frequency range 3 to 300 MHz
• 4. "Hot-Source" - hyperthermia, hot water
• 5. Laser

The Irradiation with radio waves is particularly suitable for local treatment and is adopted in Europe according to guidelines of the ESHO (European Society of Hyperthermic Oncology) (Hand, J.W. Quality Assurance Guidelines for ESHO protocols, Int. J. Hyperthermia 5, 1989, 421-428).

combinations various radiation therapies with hyperthermia, preferably generated by Microwave treatment, are known and studied (Hehr, T., Current and Potential Role of Thermoradiotherapy for Solid Tumor, Oncology, 2003, 26, 295-302; Seegenschmiedt M. H., radiotherapy and hyperthermia - a new one Way in the interdisciplinary Tumor Therapy, Yearbook Radiology (Günther ed), Springer, 161-171, 1994). The synergies of this combination therapy are currently still under investigation and not yet sufficiently documented (van der Zee J, Point-counterpoint: what is the optimal trial design to test hyperthermia for carcinoma of the cervix? Point: addition of hyperthermia or cisplatin to radiotherapy for patients with cervical cancer; two nice combinations - no definite conclusions, International journal of hyperthermia, 2002, Vol. 18 (1), 19-24).

As well The combination of hyperthermia with chemotherapy is already one in use therapy method (WO 93/18751, Liposomes encapsulated taxol and method of using the same; Kuwano H., Preoperative hyperthermia combined with chemotherapy and irradiation for the treatment of patients with esophageal carcinoma, Tumori, 1995, Vol. 81 (1), 18-22; Rietbroek RC, Hyperthermia in combination with chemotherapy in gynecological cancers, Nederlands tijdschrift voor geneeskie, 2002, Vol. 143 (2), p: 85-8; Colombo R., Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma, Journal of Clinical Oncology, 2003, Vol. 21 (23), 4270-6).

in the Principle will be in the treatment with chemo by the additional Treatment with hyperthermia postulated several positive effects: this On the one hand, improved bioavailability of the chemotherapeutic agents in the tumor by improved transport in and to the tumor and on the other hand higher Effectiveness in thermally already loaded and thus weakened tumor.

ever after tumor and chemotherapeutic can, however, different Effects also show that the additional treatment with hyperthermia shows no benefit (van Bree C., Local hyperthermic treatment does not enhance mitoxantrone effectiveness for responses of a rat solid tumor regrowing after irradiation, Journal of Cancer Research and Clinical Oncology, 1996, Vol. 122 (3), 147-53).

task The present invention is a combination of electromagnetic To provide radiation and substances which are used for prophylaxis and / or treatment of cancer, tumors and metastases.

These Task is solved by the technical teaching of the independent claims. Further advantageous embodiments, aspects and details of the invention arise from the dependent ones claims, the description and the examples.

Surprisingly was found to be a combination of radio waves and certain substances very good for the prophylaxis and treatment of cancer, tumors and metastases suitable is.

at the aforesaid Substances are preferably at least one pharmacological active substance and more preferably used in cancer therapy pharmacologically active substances.

• a) Monoklonale Antikörper und/oder
• b) Tyrosin-Kinase-Inhibitoren und/oder
• c) Angiogenese-Inhibitoren und/oder
• d) Farnesyl-Transferase-Inhibitoren und/oder
• e) Topoisomerase-I oder -II-Inhibitoren und/oder
• f) Cytokine und/oder
• g) Antisense Oligonucleotide.

In particular, these substances are active substances selected from Group comprising:

• a) monoclonal antibodies and / or
• b) tyrosine kinase inhibitors and / or
• c) angiogenesis inhibitors and / or
• d) Farnesyl transferase inhibitors and / or
• e) Topoisomerase I or II inhibitors and / or
• f) cytokines and / or
• g) antisense oligonucleotides.

To be used according to the invention therapeutic antibodies are monoclonal antibodies against Tumor cells and metastases. These include antibodies such as cetuximab, trastuzumab, Alemtuzumab, rituximab, bevacizumab, EMD7200, Rencarex, HeFi-1, Apolizumab, Tositumomab, ABX-EGF, HuMAx-EGFR, labetuzumab, pemtumomab, Triab, Mab17-1A (Panorex), MDX-210, MDX-220, MDX-447, MDX-H210, Gemtuzumab ozogamicin, radiolabeled antibodies such as indium-111 (In-111) ibritumomab Tiuxetan, yttrium-90 (Y-90) ibritumomab tiuxetan, anti-CD80 mAb, WX-G250RIT (131Jod).

Tyrosine kinase inhibitors are molecules that prevent the function of the tyrosine kinase. This can be blocked by Epidermal Growth Factor Receptor (EGFR), such as ErB-1, ErB-2 (Her2 / Neu), ErB-3, ErB-4, or other receptors of transmembrane factors such as Vascular Endothelium Growth Factor (VEGF), Fibroplasty Growth Factor (FGF), Platelet Derived Growth Factor (PDGF), Insulin Like Growth Factor (IGF-I) or Hepacotyte Growth Factor (c-met). in this connection it can be both antibodies as well as "small molecules", as examples for "small molecules "are To call gefitinib, imatinib, PKI-166, CI-1033, SU-6668.

Angiogenesis inhibitors are substances that increase the blood supply of the blood vessels Suppress the tumor. These include z. Cilengitide, Neovastat, IM862, SU5415, SU5416, SU6668 and Suramin.

Farnesyl transferase inhibitors are z. BMS214662 and R115777 (Zarnesta tipifarnib).

Examples for cytokines immunomodulators are aldesleukin, interleukin-2, interleukin-12, Interferons such as interferon alpha 2a, interferon alpha 2b, interferon beta, interferon gamma and recombinant tumor necrosis factors such as Tasonermin.

To the antisense oligonucleotides is z. B. AP12009 counted.

To be used according to the invention Chemotherapeutics are folic acid antagonists such as methotrexate, antagonists of purine and pyrimidine bases such as fluorouracil, Capecitabine, gemcitabine, cytarabine, pentostatin, cytosine arabinoside, Mercaptopurine, fludarabine, cladribine and tioguanine, alkylating Cytostatic drugs such as cyclophosphamide, ifosfamide, melphalan, thiotepa, Busulfan, cisplatin, carboplatin, oxaliplatin, procarbazine, dacarbazine, Temozolomide, etoposide, teniposide, mitotic inhibitors such as vinblastine, vincristine, Vindesine, vinorelbine, paclitaxel, docetaxel, trofosfamide, chlorambucil, Treosulfan, estramustine, nimustine, carmustine, lomustine, cytostatic Antibiotics such as dactinomycin, anthracyclines such as daunorubicin, doxorubicin (Adriamycin), doxorubicin lipo, idarubicin and epirubicin, bleomycin, mitomycins, Mitoxantrone, amsacrine, actinomycin D, hormones and hormone antagonists like Buselerin, Goselerin, Leuprorelin, Triptorelin, Anti Estrogens like tamoxifen, aromatase inhibitors like aminoglutethimide, anastrozole, Letrozole, exemestane, formestan, testolactone, glucocorticoids, other Cytostatic drugs such as miltefosine, hydroxyurea, tretinoin, topoisomerase inhibitors such as camptothecin derivatives such as irinotecan or hycamtin, topotecan or other chemotherapeutic agents such as imatinib, amsacrine, pentostatin, Bexarotene and asparaginase.

The the aforementioned chemotherapeutic agents optionally used together with the combination according to the invention become.

Surprisingly It was also found that radio waves (3 to 300 MHz) the effectiveness of certain substances for the fight against cancer, tumors and metastases increase. In many cases this happens while reducing the side effects of this Substances. As substances, the above-mentioned pharmacologically active Substances and more preferably those used in cancer therapy pharmacologically active substances and chemotherapeutic agents.

Therefore The present invention is also directed to the use of Radio waves for increasing the activity of the aforementioned substances and / or on the reduction of the side effects of the aforementioned substances.

By increasing the activity is meant, for example, the lowering of the IC ₅₀ value of a pharmacologically active substance. However, an increase in activity also means that approximately the same result is achieved with less pharmacologically active substances.

The Reduction of side effects preferably affects the chemotherapeutic agents (Cytostatics) or the side effects caused by these drugs. The side effects of chemotherapeutic agents are well suited to the expert known and pose serious problems in tumor therapy.

By the use of the combination according to the invention the prospect of a therapeutic success is significantly greater and the quality of life the patient also significantly improved.

The inventive combination is especially in the following types of cancer or tumors and metastases used: breast carcinomas, especially recurrences after radiation and chemotherapy, skin carcinomas, such as basaliomas, spinaliomas, melanomas, Skin metastases, all malignant Tumors close to the body surface soft tissue tumors, endometrial carcinoma, cervical carcinoma, ovarian cancer or ovarian carcinomas, testicular cancers or vulvar carcinomas, germ cell tumors, Prostate cancer, thyroid carcinoma, Hepatocellular carcinoma, liver metastases, colon cancer or colorectal Carcinoma, rectal cancer, lung cancer such as small cell and non-small cell lung carcinoma, lymphoma or Hodgkin's and non-Hodgkin's lymphomas, pancreatic cancer or pancreatic carcinoma, connective tissue tumor or soft tissue sarcoma, adenocarcinomas such as gastric, pancreatic, biliary-esophageal carcinomas, other gastric cancers, osteolytic carcinomas. u. osteoplastic carcinomas, renal cell carcinomas, Malignancies of the gastrointestinal tract, brain tumors such as glioblastoma, Astrocytomas, tumors of the ear, nose and throat, malignant Neoplasm, neuroblastoma, choroidal melanoma, acute leukemia, acoustic neuroma, Ampoule carcinoma, anal carcinoma, bladder cancer, breast cancer, Burkitt's lymphoma, Corpus carcinoma, CUP syndrome, small bowel cancer, Small bowel tumors Ependymoma, epithelial cancers, Ewing's tumors, gastrointestinal Tumors, gallbladder cancer, uterine cancer, Cervical cancer, gynecological Tumors, hematologic Neoplasia, hairy cell leukemia, Urethral cancer, Skin cancer, brain metastases, pituitary tumor, carcinoma, Kaposi's sarcoma, Throat cancer, bone cancer, colon carcinoma, craniopharyngioma, cancer in the mouth and on the lip, leukemia, eyelid tumors, lymphoma, rectal cancer, Medulloblastomas, melanoma, meningiomas, Hodgkin's disease, mycosis fungoides, Nasal cancer, Neurinoma, Kidney cancer, Oligodendroglioma, Esophageal carcinoma, Osteosarcoma, penile cancer, plasmocytoma, pharyngeal cancer, retinoblastoma, Sheath cancer, Schneeberger disease, T-cell lymphoma (Mycosis fungoides), Thymoma, tubal carcinoma, tumors of the eye, urethral cancer, urological Tumors, urothelial carcinoma, Wilms tumor and tongue cancer.

at the combination according to the invention the radio waves are in a frequency range of 3 to 30 MHz, preferably 5 to 20 MHz, and more preferably 10 to 15 MHz. Particularly preferred is a frequency of 13.56 MHz. Further will be the radio waves preferably generated by capacitive coupling.

Of Furthermore, the present invention relates to a method for prophylaxis and / or treatment of cancer, tumors and / or metastases Application of the combination according to the invention. The tumors are preferably cancerous and benign Tumors.

• a) Monoklonale Antikörper und/oder
• b) Tyrosin-Kinase-Inhibitoren und/oder
• c) Angiogenese-Inhibitoren und/oder
• d) Farnesyl-Transferase-Inhibitoren und/oder
• e) Topoisomerase-I oder-II-Inhibitoren und/oder
• f) Cytokine und/oder
• g) Antisense Oligonucleotide

eingesetzt. Dabei wird das Radiowellenfeld bevorzugt extratumoral angelegt.In this method for the prophylaxis and / or treatment of cancer, tumors and / or metastases, radio waves in combination with at least one active substance are selected from the group

• a) monoclonal antibodies and / or
• b) tyrosine kinase inhibitors and / or
• c) angiogenesis inhibitors and / or
• d) Farnesyl transferase inhibitors and / or
• e) topoisomerase I or II inhibitors and / or
• f) cytokines and / or
• g) antisense oligonucleotides

used. The radio wave field is preferably created extratumoral.

As already mentioned, can additionally to the administration of one or more of the active substances mentioned under (a) - (g) or more chemotherapeutic agents are applied.

The Chemitherapeutika are preferred from the group listed above selected. at under a) - g) mentioned agents are also the aforementioned in question.

The Radio wave field is preferably generated by capacitive coupling and is also preferred extratumoral created. Treatment with Radio waves is done with devices, which generate the radio wave field by a capacitive coupling. In capacitive coupling, the tissue is between two Electrodes over an AC power source are fed and as capacitor plates serve. Between these electrodes, the electromagnetic builds Field in the form of a medium-wave radio wave on.

The Radio wave field is preferably applied extratumoral, especially preferably extratumoral and extracorporeal. That is, usually No invasive surgery is needed to treat radio waves being difficult to access Tumors also brought invasive electrodes near the tumor can be.

The Frequencies of the radio waves or the radio wave field are in Range from 3 to 30 MHz, preferably from 5 to 20 MHz, especially preferably from 10 to 15 MHz, and more preferably at 13.56 MHz, i. at the frequency approved in Europe by telecommunications for such Applications.

at The method described may be the irradiation with radio waves and the application of the active ingredient simultaneously or with a time delay takes place, being between the administration of the active substance and the treatment with radio waves 72 hours, preferably 48 hours and more preferred less than 24 hours.

ever After indication, it is preferable to irradiation with radio waves at the same time as the administration of the active substance or delayed. The preferred periods for the time-shifted application of irradiation and application of the drug are 12, 24, 36, 48, 60 and 72 hours, with 24, 48 and 72 hours in particular are preferred. For the expert requires only a few experiments, the optimal sequence of irradiation and administration of the at least one active substance possibly together with at least one chemotherapeutic find out.

Further can also the at least one mentioned under a) to g) active ingredient at the same time or staggered with the at least one chemotherapeutic agent become. The time difference can be between the fraction of a Hour to a few days. However, the simultaneous is preferred Administration.

The Active ingredients and chemotherapeutic agents are used in conventional formulations and preferably applied systemically.

Claims (16)

Combination of radio waves with at least one Active ingredient selected from the group a) monoclonal antibodies and / or b) Tyrosine Kinase Inhibitors and or c) angiogenesis inhibitors and / or d) Farnesyl transferase inhibitors and or e) topoisomerase I or II inhibitors and / or f) Cytokines and / or g) antisense oligonucleotides. A combination according to claim 1, further comprising at least one chemotherapeutic agent. A combination according to claim 2, wherein the at least one chemotherapeutic agent for folic acid antagonists, methotrexate, Antagonists of purine and pyrimidine bases, fluorouracil, capecitabine, Gemcitabine, cytarabine, pentostatin, cytosine arabinoside, mercaptopurine, Fludarabine, cladribine and tioguanine, alkylating cytostatic drugs, cyclophosphamide, Ifosfamide, melphalan, thiotepa, busulfan, cisplatin, carboplatin, Oxaliplatin, procarbazine, dacarbazine, temozolomide, etoposide, teniposide, Mitotic inhibitors, vinblastine, vincristine, vindesine, vinorelbine, Paclitaxel, docetaxel, trofosfamide, chlorambucil, treosulfan, estramustine, Nimustine, carmustine, lomustine, cytostatic antibiotics such as dactinomycin, anthracyclines, daunorubicin, doxorubicin (adriamycin), Doxorubicin lipo, idarubicin, epirubicin, bleomycin, mitomycins, Mitoxantrone, amsacrine, actinomycin D, hormones and hormone antagonists, Buselerin, Goselerin, Leuprorelin, Triptorelin, Antiestrogens, Tamoxifen, aromatase inhibitor, aminoglutethimide, anastrozole, letrozole, Exemestane, formestan, testolactone, glucocorticoids, miltefosine, Hydroxyurea, tretinoin, topoisomerase inhibitors, camptothecin derivatives, Irinotecan, Hycamtin, Topotecan, Imatinib, Amsacrine, Pentostatin, Bexarotene and asparaginase. Combination according to any one of claims 1-3, wherein the radio waves in the frequency range of 3 to 30 MHz, preferably 5 to 20 MHz and 10 to 15 MHz are particularly preferred. A combination as claimed in any one of claims 1 to 4, wherein the radio waves formed radio wave field is generated by capacitive coupling. Combination according to any one of claims 1-5, wherein the monoclonal Antibody, Tyrosine Kinase Inhibitors, Angiogenesis Inhibitors, Farnesyl Transferase Inhibitors, Topoisomerase I inhibitors, topoisomerase II inhibitors, cytokines and / or antisense Oligonucleotides selected are selected from the group comprising cetuximab, trastuzumab, alemtuzumab, Rituximab, Bevacizumab, EMD7200, Rencarex, HeFi-1, Apolizumab, Tositumomab, ABX-EGF, HuMAx-EGFR, labetuzumab, pemtumomab, triab, Mab17-1A (panorex), MDX-210, MDX-220, MDX-447, MDX-H210, gemtuzumab, ozogamicin, radiolabelled Antibody, Indium-111 (In-111) ibritumomab tiuxetan, yttrium-90 (Y-90) ibritumomab Tiuxetan, anti-CD80 mAb, WX-G250RIT (131 iodine), gefitinib, imatinib, PKI-166, CI-1033, SU-6668, Cilengitide, Neovastat, IM862, SU5415, SU5416, Suramin, BMS214662, R115777 (Zarnesta tipifarnib), aldesleukin, interleukin-2, interleukin-12, interferons, Interferon alpha 2a, interferon alpha 2b, interferon beta, interferon gamma, tasonermin, AP12009. Use of the combination according to one of claims 1 to 6 for Prophylaxis and / or treatment of cancer, cancerous and / or benign tumors and metastases. Use according to claim 7 wherein the cancer, tumors and metastases are breast carcinomas, especially recurrences after radiotherapy and chemotherapy, skin carcinomas such as basaliomas, spinaliomas, melanomas, skin metastases, all malignant tumors close to the body surface, soft tissue tumors , Endometrial carcinoma, cervical carcinoma, ovarian cancer or ovarian carcinomas, testicular or vulvar carcinomas, germ cell tumors, prostate carcinomas, thyroid carcinomas, hepatocellular carcinomas, liver metastases, colorectal carcinoma, rectal carcinoma, lung cancer such as small and non-small cell lung carcinoma, lymph node carcinoma or Hodgkin's and non-Hodgkin's lymphoma, pancreatic cancer or pancreatic carcinoma , Connective tissue tumor or soft tissue sarcoma, adenocarcinomas such as gastric, pancreatic, biliary esophageal carcinomas, other gastric carcinomas, osteolytic carcinomas. u. osteoplastic carcinomas, renal cell carcinomas, gastrointestinal tract malignancies, brain tumors such as glioblastoma, astrocytomas, tumors of the ear, nose and throat, malignant neoplasm, neuroblastoma, choroidal melanoma, acute leukemia, acoustic neuroma, ampoule carcinoma, anal carcinoma, bladder cancer, breast cancer, Burkitt's disease Lymphoma, corpus carcinoma, CUP syndrome, small bowel cancer, small intestinal tumors, ependymoma, epithelial cancers, Ewing tumors, gastrointestinal tumors, gall bladder cancer, uterine cancer, cervix cancer, gynecological tumors, hematologic neoplasia, hairy cell leukemia, urethral cancer, skin cancer, brain metastasis, pituitary tumor, carcinode , Kaposi's sarcoma, cancer of the throat, bone cancer, colon carcinoma, craniopharyngioma, cancer of the mouth and on the lip, leukemia, eyelid tumors, lymphoma, rectal cancer, medulloblastoma, melanoma, meningioma, Hodgkin's disease, mycosis fungoides, nasal cancer, neuroma, kidney cancer, oligodendroglioma, esophageal carcinoma , Osteosarcoma, Peni cancer, plasmocytoma, pharyngeal cancer, retinoblastoma, vaginal cancer, Schneeberger's disease, T-cell lymphoma (mycosis fungoides), thymoma, tubal cancer, tumors of the eye, urethral cancer, urological tumors, urothelial carcinoma, Wilms tumor and / or tongue cancer. Use according to claim 7 or 8, wherein the radio waves at the same time as the active ingredient or up to 72 hours, preferably 48 Hours, and more preferably delayed up to 24 hours be used. Use according to any one of claims 7-9, wherein the radio waves generated radio wave field is applied extratumoral. Use of radio waves to increase the activity of a Active substance selected from the group comprising a) monoclonal antibodies and / or b) Tyrosine Kinase Inhibitors and / or c) angiogenesis inhibitors and or d) Farnesyl transferase inhibitors and / or e) Topoisomerase I or II inhibitors and / or f) cytokines and / or G) Antisense oligonucleotides and / or h) chemotherapeutic agents. Use of radio waves to reduce side effects of chemotherapeutic agents. Use according to any one of claims 11 or 12, wherein the chemotherapeutic agents to be selected from the group comprising: folic acid antagonists, Methotrexate, antagonists of purine and pyrimidine bases, fluorouracil, Capecitabine, gemcitabine, cytarabine, pentostatin, cytosine arabinoside, Mercaptopurine, fludarabine, cladribine and tioguanine, alkylating Cytostatics, cyclophosphamide, ifosfamide, melphalan, thiotepa, busulfan, Cisplatin, carboplatin, oxaliplatin, procarbazine, dacarbazine, temozolomide, Etoposide, teniposide, mitotic inhibitors, vinblastine, vincristine, vindesine, Vinorelbine, paclitaxel, docetaxel, trofosfamide, chlorambucil, treosulfan, estramustine, Nimustine, carmustine, lomustine, cytostatic antibiotics such as dactinomycin, anthracyclines, daunorubicin, doxorubicin (adriamycin), doxorubicin lipo, idarubicin, epirubicin, bleomycin, mitomycins, mitoxantrone, Amsacrine, actinomycin D, hormones and hormone antagonists, Buselerin, Goselin, leuprorelin, triptorelin, antiestrogens, tamoxifen, aromatase inhibitors, Aminoglutethimide, anastrozole, letrozole, exemestane, formestan, testolactone, Glucocorticoids, miltefosine, hydroxyurea, tretinoin, topoisomerase inhibitors, Camptothecin derivatives, irinotecan, hycamtin, topotecan, imatinib, Amsacrine, pentostatin, bexarotene and asparaginase. Use according to any one of claims 11-13, wherein the monoclonal Antibody, Tyrosine Kinase Inhibitors, Angiogenesis Inhibitors, Farnesyl Transferase Inhibitors, Topoisomerase I inhibitors, topoisomerase II inhibitors, cytokines and / or antisense Oligonucleotides selected are selected from the group comprising cetuximab, trastuzumab, alemtuzumab, Rituximab, Bevacizumab, EMD7200, Rencarex, HeFi-1, Apolizumab, Tositumomab, ABX-EGF, HuMAx-EGFR, labetuzumab, pemtumomab, triab, Mab17-1A (panorex), MDX-210, MDX-220, MDX-447, MDX-H210, gemtuzumab, ozogamicin, radiolabelled Antibody, Indium-111 (In-111) ibritumomab tiuxetan, yttrium-90 (Y-90) ibritumomab Tiuxetan, anti-CD80 mAb, WX-G250RIT (131 iodine), gefitinib, imatinib, PKI-166, CI-1033, SU-6668, Cilengitide, Neovastat, IM862, SU5415, SU5416, Suramin, BMS214662, R115777 (Zarnesta tipifarnib), aldesleukin, interleukin-2, interleukin-12, interferons, Interferon alpha 2a, interferon alpha 2b, interferon beta, interferon gamma, tasonermin, AP12009. Use according to any of claims 11-14, wherein the radio waves in the frequency range of 3 to 30 MHz, preferably 5 to 20 MHz and 10 to 15 MHz are particularly preferred. Method for the prophylaxis and / or treatment of Cancer, tumors and / or metastases, by combining radio waves with at least one active ingredient selected from the group a) Monoclonal antibodies and or b) tyrosine kinase inhibitors and / or c) angiogenesis inhibitors and or d) Farnesyl transferase inhibitors and / or e) Topoisomerase I or II inhibitors and / or f) cytokines and / or G) Antisense oligonucleotides be used.